Cardiovascular death and morbidity continue to be major long-term complications in renal transplant patients. Abnormalities in lipids and lipoproteins may partially contribute to the increased risk; however, other risk factors may be involved. Homocysteine is rapidly emerging as an important risk factor for the development of coronary, carotid and peripheral atherosclerotic events. There is early evidence that elevated homocysteine levels commonly occur in patients with renal transplants or chronic renal disease, but the appropriate diagnostic or therapeutic approaches have not been established. The proposed studies include: 1.) The frequency and severity of hyper-homocysteinemia and the appropriate diagnostic approach will be evaluated. 2.)The causes of hyper-homocysteinemia will be evaluated. They will include the influence of renal function, nutritional, genetic and concomitant medication. 3.) Therapeutic approaches to normalize both fasting and post-methionine load homocysteine levels will be evaluated. 4.) The overall goal will be to develop simple clinical algorithms for the diagnosis and treatment of homocysteine disorders.